Steroid-Responsive Esophageal Obstruction in a Child with Chronic Granulomatous Disease (CGD)

Abstract

Chronic granulomatous disease (CGD) is an inherited condition characterized by recurrent pyogenic infections and granuloma formation. CGD is associated with granulomatous obstruction of the gastrointestinal tract, most commonly antral narrowing (1-4). Esophageal obstruction is rare, with only four reported cases. The treatment is controversial, with both antibiotics and corticosteroids reported as effective. We report successful corticosteroid treatment of an esophageal obstruction in the youngest patient with CGD reported to date. CASE REPORT A 3-year-old Latin-American boy with CGD was seen in Texas Children's Hospital with a 4-day history of dysphagia that was relieved by vomiting. Initially the vomiting occurred only after eating solids but eventually progressed to liquids as well. The vomitus was always nonbilious, without blood, and occurred within 2 to 3 min after swallowing. There was no fever, heartburn, abdominal pain, or decreased appetite. His medical history was significant for intermittent vomiting over the prior 6 months, as well as multiple pyogenic infections, including pneumonia, sinusitis, and liver and perirectal abscesses. Chronic granulomatous disease (X-linked form) was diagnosed when he was 4 months old and had pneumonia with pneumatocoele/abscess. Neutrophil studies showed 0% nitroblue tetrazolium (NBT) dye reduction, absent in vitro superoxide production, and markedly diminished phagocytosis-associated chemiluminescence. He has a maternal first cousin with CGD who demonstrated similar in vitro study results at our institution. Our patient's mother, maternal grandmother, and two maternal aunts had NBT tests ranging from 58 to 87% positive cells, consistent with X-linked carrier status. Two maternal aunts had normal NBT tests (100% dye reduction) and therefore were not carriers. On admission to Texas Children's Hospital, his vital signs were temperature, 37.6°C; pulse, 114; respiratory rate, 26; blood pressure, 100/70; and weight, 12.6 kg. The patient was thirsty, vomited immediately after taking sips of water, and appeared mildly dehydrated but had moist mucous membranes and tearing. The abdomen was soft and nontender, with no palpable masses or organomegaly. Rectal examination revealed two draining, nonerythematous perirectal sinuses. The remainder of his physical examination was unremarkable. The white cell count was 10,000/mm with 75% polymorphonuclear leukocytes, 18% lymphocytes, and 7% mononuclear cells. Hemoglobin was 10.8 g/dl, and platelets, 347,000/mm. The serum sodium was 143 mM/L; potassium, 4.3 mM/L; chloride, 105 mM/L; and bicarbonate, 18 mM/L. Urinalysis was significant for a specific gravity of 1.32 with 3 + ketones. Upper gastrointestinal series (UGI) revealed a persistent midesophageal narrowing on fluoroscopy (Fig. 1). The patient was admitted with a diagnosis of mild dehydration and gastroesophageal reflux. His mild dehydration was corrected with i.v. fluids. On hospital day 2, an upper endoscopy was performed using a 9-mm Pentax 2700 series endoscope (Pentax Precision Instrument Corporation, Orangeburg, NY, U.S.A.), which revealed a tight stenosis of the esophagus at 15 cm from the incisors, through which the scope would not pass (Fig. 2). The mucosa appeared nodular and edematous, and no Barrett's-like mucosa was seen (Fig. 2). An 8-mm balloon dilator (Microvasive, Watertown, MA, U.S.A.) was easily passed and inflated for 2 min, followed by a 10-mm and a 12-mm balloon in the same manner. However, the scope would still not pass through the narrowing. A trial with a smaller 7.9-mm Pentax FG 2400 endoscope was also unsuccessful. Several biopsies were obtained from the stenotic area. Biopsies revealed esophageal mucosa with a moderate number of intraepithelial eosinophils, basal cell hyperplasia, and extension of the papillae into the more superficial layers of the epithelium; a diagnosis of reflux esophagitis was made. Viral, bacterial, and fungal cultures were all negative. The patient was started on ranitidine, 2 mg/kg/dose three times daily, and metoclopramide, 0.15 mg/kg/dose four times daily. Over a 3-day period, he tolerated clear liquids and was advanced to a soft mechanical diet, which he tolerated well. He was discharged home taking ranitidine, metoclopramide, and reflux precautions in good condition. He did well at home for only 3 days. He returned to Texas Children's Hospital with 1-day history of vomiting and intolerance of liquids by mouth. The parents denied noncompliance with medications. On physical examination, he was again mildly dehydrated, without fever and with normal vital signs. His serum sodium was 143 mM/l; potassium, 4.0 mM/L; bicarbonate, 11 mM/L; BUN, 24 mg/dl; creatinine, 0.5 mM/L, and erythrocyte sedimentation rate (ESR), 54 mm/h. He was placed on intravenous fluids; ranitidine and metoclopramide were continued. Barium swallow again revealed a persistent midesophageal narrowing. The reflux treatment was deemed unsuccessful, and a tentative diagnosis of esophageal stricture secondary to CGD was made. The patient had no history of recent fever; therefore, intravenous methylprednisolone was started at 1 mg/kg/day for 3 days followed by oral prednisone 1.2 mg/kg/day. Dramatic improvement of his swallowing was noted within 48 h. Repeat barium swallow after 5 days was normal (Fig. 3). After 1 week, the patient was discharged home with prednisone, ranitidine, and metoclopramide. Prednisone was tapered over a 2-month period. One month after stopping prednisone, the patient had recurrent emesis with difficulty swallowing. Repeat barium swallow showed recurrence of the midesophageal narrowing (Fig. 4). Prednisone was restarted at 1mg/kg/day for 1 month, then slowly over a 3-month period. Repeat barium swallow showed marked improvement with slight esophageal narrowing, and the patient has remained free of stricture symptoms for 18 months (Fig. 5). At 4 months following the resolution of the stricture, however, the patient developed a pulmonary lesion. A biopsy study was performed, and Nocardia grew in culture. The patient has subsequently been treated with Bactrim and Clindamycin and is asymptomatic from a pulmonary standpoint. DISCUSSION CGD belongs to a group of disorders of the oxidative metabolism of phagocytes, and is inherited primarily in an X-linked manner, but may also be autosomal recessive. CGD is characterized by the impairment of intracellular killing of catalase-positive bacteria, fungi, or other microbes. The basis for abnormal oxygen-dependent microbicidal activity in CGD phagocytes is related to deficiency in respiratory burst oxidase activity and impaired generation of superoxide anion. The hallmark of CGD is recurrent infection of the skin, reticuloendothelial organs, and lungs resulting in abscess and granuloma formation (5). Gastrointestinal manifestations of CGD include perianal abscesses or fistulas (6), esophageal dysmotility (7), gastric outlet obstruction (3,4), small bowel obstruction (8), and granulomatous colitis with recurrent abdominal pain. Only four cases of esophageal obstruction associated with CGD have been reported (4,10). Chin et al. (4) reported a 10-year-old boy with CGD diagnosed with esophageal narrowing by barium swallow but no endoscopy. No infectious cause was found. A trial with antibiotics and esophageal dilation was unsuccessful, but treatment with prednisone resulted in dramatic clinical and radiologic improvement. Renner et al. (10) reported three patients with esophageal stricture secondary to CGD. All patients had esophageal biopsies showing nonspecific inflammation and no evidence of infection or granuloma. Two of these patients were successfully treated with multiple balloon dilations. One patient, however, developed esophageal stricture while receiving 5 mg of prednisone a day and subsequently demonstrated only partial and temporary response to two separate trials of high-dose steroids. Although our patient's esophageal stricture resolved with prednisone and antireflux therapy, he subsequently developed pulmonary infection with Nocardia. This infection is not uncommon in CGD and may or may not have been potentiated by the prior use of steroids. Other cases of CGD with granulomatous obstruction treated with steroids have not reported infectious complications at doses of ≤1 mg/kg/day for short periods (4,11). The role of corticosteroids versus antibiotics in the management of esophageal stricture in CGD remains controversial. In our case, the esophageal biopsies were diagnostic of gastroesophageal reflux. The patient, however, failed to respond to standard reflux treatment. Cultures and histologic studies excluded infection. The exact cause of the esophageal inflammation and stricture was not established in our case or any other reported cases. Given the recurrent nature of the esophageal filling defect, the successful response to corticosteroids and tendency for granuloma formation in CGD, this is most likely secondary to local granuloma formation. Granulomas could have formed deep in the intramuscular layer of the esophagus, which would have been beyond the reach of a routine endoscopic biopsy. Our patient demonstrated symptomatic and radiologic improvement within 1 week of prednisone therapy on two occasions. In summary, we report an esophageal obstruction secondary to CGD, successfully treated with prednisone in a 3-year-old child. We suggest corticosteroid treatment be cautiously considered, once infection has been ruled out, even in the absence of granuloma on esophageal biopsy.FIG. 1.: Admission upper gastrointestinal series (UGI), showing mild midesophageal narrowing.FIG. 2.: Endoscopic view of the esophagus, showing tight stenosis. The mucosa appears nodular and edematous.FIG. 3.: Upper gastrointestinal series 5 days after steroid therapy, showing normal esophagus with disappearance of midesophageal narrowing.FIG. 4.: Upper gastrointestinal series 1 month after stopping steroids, showing recurrence of midesophageal narrowing.FIG. 5.: Upper gastrointestinal series 2 months after steroid therapy, showing marked improvement, with the presence of residual slight esophageal narrowing.